Clinical Impact of Drug Use in HIV-Infected Persons: A Pilot Study

描述（由申请人提供）：药物滥用在俄罗斯的艾滋病毒流行中起着突出作用；近80%的病例归因于注射吸毒。药物使用史或在艾滋病毒诊断后继续使用可导致负面健康后果。药物使用可能会阻碍患者接受包括抗逆转录病毒治疗在内的医疗护理的努力。药物滥用对艾滋病毒疾病进展的直接生理影响尚未得到明确记录，尽管免疫学研究结果表明这种关联具有合理基础。因此，与吸毒有关的各种因素可能使感染艾滋病毒的吸毒者面临更大的艾滋病毒疾病快速进展的风险。然而，药物滥用与艾滋病毒疾病进展之间存在独立关联的明确证据有待进一步研究。这项研究计划的主要目标是调查药物滥用与艾滋病毒疾病进展之间的关系，方法是利用目前正在开发的俄罗斯700名艾滋病毒感染成人队列，其中许多人以前有注射吸毒史。这项为期一年的R21试点研究“药物使用影响”（在队列试验中调查和测量艾滋病进展）将为设计未来的纵向研究计划奠定重要基础，该计划可以更明确地评估药物使用与艾滋病疾病进展之间的关系。具体目标是：1。使用现有的俄罗斯HIV感染者队列来评估HIV疾病进展的标志物（即CD4细胞计数、HIV病毒载量[HIV RNA]）和混杂因素。2. 估计药物使用对HIV疾病进展标志物的影响大小，控制ART使用、基线CD4细胞计数、HIV RNA（用于CD4结果）、酒精使用、抑郁和社会人口统计学。3. 探索药物使用加剧艾滋病毒疾病进展的潜在机制（例如，减少获得抗逆转录病毒治疗、增加酒精使用、抑郁和丙型肝炎病毒合并感染）。我们将从现有的NIH研究中招募100名受试者，并收集关于药物依从性和药物使用的额外自我报告数据。我们将收集生物样本来评估CD4细胞计数、HIV RNA和药物使用（所有样本的尿液毒理学和亚样本的头发毒理学）。这些数据将与已有的队列数据（如酒精使用、人口统计数据）相结合。我们假设，通过CD4细胞计数和HIV病毒载量测量，非法药物使用与更快速的HIV疾病进展独立相关。这项研究产生的数据将使我们能够对这一假设进行初步检验。具体而言，它将提供重要的效应量估计，这将有助于设计未来的队列研究，该研究将对受试者进行数年的纵向跟踪，以充分表征药物滥用与艾滋病毒疾病进展之间的关系。主要分析将是当前的药物使用情况；然而，特定药物使用特征（即特定药物，给药途径，暴露时间）的影响将在二次分析中探讨。有证据表明药物使用与艾滋病毒病情恶化之间存在关系，但在美国对这种关系的研究由于几个重要的混杂因素而变得复杂：在30年前的流行病中，未知的个人艾滋病毒感染持续时间；经常使用多种药物；长期使用带有相关病毒耐药菌株的抗逆转录病毒治疗；以及普遍使用抗逆转录病毒药物，这对艾滋病毒疾病进展有主要影响。在目前的俄罗斯环境中，这些混杂因素中的每一个都得到了缓解，使其成为一个有希望的地点，可以研究药物使用与艾滋病毒疾病进展之间的关系，以及可能介导这种关系的潜在途径。阐明药物使用与艾滋病毒疾病进展的关系将有助于临床医生、公共卫生专业人员和政策制定者努力改善医疗保健、成瘾治疗，并最终改善感染艾滋病毒的吸毒者的健康状况。

DESCRIPTION (provided by applicant): Drug abuse plays a prominent role in the HIV epidemic in Russia; nearly 80% of cases are attributed to injection drug use. A history of drug use or continued use after an HIV diagnosis can lead to negative health consequences. Drug use may hinder efforts to engage patients in medical care including use of antiretroviral treatment (ART). A direct physiologic impact of drugs of abuse on HIV disease progression has not been clearly documented despite immunologic findings suggesting a rational basis for such an association. Hence, a variety of factors associated with drug use may place the HIV-infected drug user at increased risk for more rapid HIV disease progression. However, clear evidence of an independent association between drug abuse and HIV disease progression awaits further study. The primary goal of this research initiative is to investigate the relationship between drug abuse and HIV disease progression by utilizing a currently developing cohort of 700 HIV-infected adults in Russia, many with a prior history of injection drug use. This 1-year R21 pilot study, "Drug Use IMPACT" (Investigating and Measuring Progression to AIDS in a Cohort Trial), will lay important groundwork for the design of a future longitudinal research initiative that can more definitively assess the relationship between drug use and HIV disease progression. The Specific Aims are: 1. Use an existing cohort of HIV-infected Russians to assess markers of HIV disease progression (i.e., CD4 cell count, HIV viral load [HIV RNA]) and confounding factors. 2. Estimate the effect size of drug use on markers of HIV disease progression, controlling for ART use, baseline CD4 cell count, HIV RNA (for CD4 outcome), alcohol use, depression, and sociodemographics. 3. Explore potential mechanisms by which drug use worsens HIV disease progression (e.g. reduced access to ART, increased alcohol use, depression, and HCV co-infection). We will recruit 100 subjects from an existing NIH study and collect additional self-report data on medication adherence and drug use. We will collect biological samples to assess CD4 cell count, HIV RNA, and drug use (urine toxicology on all and hair toxicology on a subsample). These data will be combined with data already available on the cohort (e.g. alcohol use, demographics). We hypothesize that illicit drug use is independently associated with more rapid HIV disease progression, as measured by CD4 cell count and HIV viral load. The data generated from this study will allow us to conduct preliminary tests of this hypothesis. Specifically, it will provide important effect size estimates that will be useful for designing a future cohort study that follows subjects longitudinally over several years to fully characterize the relationship between drug abuse and HIV disease progression. The primary analysis will be on any current drug use; however, the effects of specific drug use characteristics (i.e., specific drug, route of administration, exposure duration) will be explored in secondary analyses. Evidence suggests a relationship between drug use and worse HIV disease progression but the study of this relationship in the United States is complicated by several important confounders: unknown individual duration of HIV infection in an epidemic three decades old; substance use that frequently involves multiple drugs; longstanding use of ART with associated viral resistant strains; and common ART use which has a dominant effect on HIV disease progression. Each of these confounders is mitigated in the current Russian setting, making it a promising site to examine both the association between drug use and HIV disease progression, and the potential pathways that may mediate such a relationship. Elucidation of the relationship of drug use to HIV disease progression will facilitate efforts by clinicians, public health professions, and policy makers to improve the medical care, addiction treatment, and ultimately the health status of HIV-infected drug users.